Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase

Jing GUO; Jihong ZHENG; Ruixia LI; Jindong YAO; He ZHANG; Xu WANG; Chao ZHANG

doi:10.1631/jzus.B2400099

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Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase

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Research Article | Updated：2025-06-24

Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase
Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase
单细胞转录组分析揭示印迹基因谷氨酰基环化酶缺失导致异常的血管生成和胎盘形成
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 6, Pages: 589-608(2025)
Affiliations：

1.Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
2.Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201306, China
3.Obstetrics & Gynecology Hospital of Fudan University, Fudan University School of Medicine, Shanghai 200433, China
4.Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
5.Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
6.HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA
Funds：
DOI：10.1631/jzus.B2400099
CLC：
CSTR：
Received：25 February 2024，

Revised：08 August 2024，

Published：15 June 2025
Accepted：

郭婧,郑继红,李瑞霞等.单细胞转录组分析揭示印迹基因谷氨酰基环化酶缺失导致异常的血管生成和胎盘形成[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(06):589-608.

Jing GUO, Jihong ZHENG, Ruixia LI, et al. Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(6): 589-608.
郭婧,郑继红,李瑞霞等.单细胞转录组分析揭示印迹基因谷氨酰基环化酶缺失导致异常的血管生成和胎盘形成[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(06):589-608. DOI： 10.1631/jzus.B2400099.

Jing GUO, Jihong ZHENG, Ruixia LI, et al. Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(6): 589-608. DOI： 10.1631/jzus.B2400099.

摘要

印迹基因在哺乳动物胎盘和胚胎发育的调控中起重要作用。本研究利用CRISPR/Cas9技术系统，构建了谷氨酰基环化酶

Qpct

基因敲除小鼠，并确定

Qpct

是调控小鼠胎盘形成中的一个新抗血管生成基因。与

Qpct

+/+

小鼠相比，

Qpct

‒/+

和

Qpct

‒/‒

小鼠的胎盘和胚胎在E12.5、E15.5和E18.5时表现出明显的过度生长。本研究对32 309个来自

Qpct

+/+

和

Qpct

‒/‒

小鼠胎盘的细胞进行单细胞转录组分析，利用snRNA-seq技术鉴定了13个细胞群（包括8880个

Qpct

+/+

细胞和13 577个

Qpct

‒/‒

细胞），并通过scRNA-seq技术识别出20个细胞群（包括6567个

Qpct

+/+

细胞和3285个

Qpct

‒/‒

细胞）。此外，本研究观察到

Qpct

‒/‒

小鼠中促血管生成基因的表达水平上调。免疫组化分析显示，在E15.5的

Qpct

‒/+

和

Qpct

‒/‒

小鼠的蜕膜层和迷宫层中，血管数量显著增加。此外，在蜕膜层、内皮细胞和巨噬细胞中，多种受体-配体对的相互作用增强，促进了血管生成和炎症反应。本研究结果表明，母本

Qpct

缺失可导致胎盘和胚胎的表型特征发生改变，并促进小鼠胎盘中血管的生成。

Abstract

Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here

we generated glutaminyl-peptide cyclotransferase-knockout (

Qpct

-/-

) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified

Qpct

as a novel anti-angiogenic factor in regulating mouse placentation. Compared with

Qpct

+/+

mice

placentae and embryos (

Qpct

-/+

and

Qpct

-/-

) showed signi

ficant overgrowth at embryonic Day 12.5 (E12.5)

E15.5

and E18.5. Using single-cell transcriptome analysis of 32 309 cells from

Qpct

+/+

and

Qpct

-/-

mouse placentae

we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880

Qpct

+/+

and 13 577

Qpct

-/-

cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567

Qpct

+/+

and 3285

Qpct

-/-

cells). Furthermore

we observed a global up-regulation of pro-angiogenic genes in the

Qpct

-/-

background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5

Qpct

-/+

and

Qpct

-/-

mice. Moreover

the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells

endothelial cells

and macrophages

promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal

Qpct

leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.

关键词

Keywords

references

Abu El-Asrar AM , Ahmad A , Siddiquei MM , et al. , 2019 . The proinflammatory and proangiogenic macrophage migration inhibitory factor is a potential regulator in proliferative diabetic retinopathy . Front Immunol , 10 : 2752 . https://doi.org/10.3389/fimmu.2019.02752 https://doi.org/10.3389/fimmu.2019.02752

Arauzo-Bravo MJ , Delic D , Gerovska D , et al. , 2020 . Protective vaccination reshapes hepatic response to blood-stage malaria of genes preferentially expressed by NK cells . Vaccines (Basel) , 8 ( 4 ): 677 . https://doi.org/10.3390/vaccines8040677 https://doi.org/10.3390/vaccines8040677

Bartolomei MS , Zemel S , Tilghman SM , 1991 . Parental imprinting of the mouse H19 gene . Nature , 351 : 153 - 155 . https://doi.org/10.1038/351153a0 https://doi.org/10.1038/351153a0

Bode S , Peters C , Deussing JM , 2005 . Placental cathepsin M is alternatively spliced and exclusively expressed in the spongiotrophoblast layer . Biochim Biophys Acta , 1731 ( 3 ): 160 - 167 . https://doi.org/10.1016/j.bbaexp.2005.10.005 https://doi.org/10.1016/j.bbaexp.2005.10.005

Bullerwell CE , Robichaud PP , Deprez PML , et al. , 2021 . EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLLH3K4 methyltransferase complex . Sci Rep , 11 : 1537 . https://doi.org/10.1038/s41598-021-81000-5 https://doi.org/10.1038/s41598-021-81000-5

Busby WH , Quackenbush GE , Humm J , et al. , 1987 . An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes . J Biol Chem , 262 ( 18 ): 8532 - 8536 . https://doi.org/10.1016/S0021-9258(18)47446-7 https://doi.org/10.1016/S0021-9258(18)47446-7

Carbone C , Piro G , Merz V , et al. , 2018 . Angiopoietin-like proteins in angiogenesis, inflammation and cancer . Int J Mol Sci , 19 ( 2 ): 431 . https://doi.org/10.3390/ijms19020431 https://doi.org/10.3390/ijms19020431

Charalambous M , Cowley M , Geoghegan F , et al. , 2010 . Maternally-inherited Grb10 reduces placental size and efficiency . Dev Biol , 337 ( 1 ): 1 - 8 . https://doi.org/10.1016/j.ydbio.2009.10.011 https://doi.org/10.1016/j.ydbio.2009.10.011

Chen H , Detmer SA , Ewald AJ , et al. , 2003 . Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development . J Cell Biol , 160 ( 2 ): 189 - 200 . https://doi.org/10.1083/jcb.200211046 https://doi.org/10.1083/jcb.200211046

Chen M , Yi B , Zhu N , et al. , 2016 . Pim1 kinase promotes angiogenesis through phosphorylation of endothelial nitric oxide synthase at Ser-633 . Cardiovasc Res , 109 ( 1 ): 141 - 150 . https://doi.org/10.1093/cvr/cvv250 https://doi.org/10.1093/cvr/cvv250

Cleaton MA , Dent CL , Howard M , et al. , 2016 . Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction . Nat Genet , 48 ( 12 ): 1473 - 1480 . https://doi.org/10.1038/ng.3699 https://doi.org/10.1038/ng.3699

Dalangood S , Zhu Z , Ma Z , et al. , 2020 . Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer . Theranostics , 10 ( 22 ): 10078 - 10091 . https://doi.org/10.7150/thno.48711 https://doi.org/10.7150/thno.48711

Desdin-Mico G , Soto-Heredero G , Aranda JF , et al. , 2020 . T cells with dysfunctional mitochondria induce multimorbidity and premature senescence . Science , 368 ( 6497 ): 1371 - 1376 . https://doi.org/10.1126/science.aax0860 https://doi.org/10.1126/science.aax0860

Ding J , Adiconis X , Simmons SK , et al. , 2020 . Systematic comparison of single-cell and single-nucleus RNA-sequencing methods . Nat Biotechnol , 38 : 737 - 746 . https://doi.org/10.1038/s41587-020-0465-8 https://doi.org/10.1038/s41587-020-0465-8

Doherty AS , Mann MR , Tremblay KD , et al. , 2000 . Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo . Biol Reprod , 62 ( 6 ): 1526 - 1535 . https://doi.org/10.1095/biolreprod62.6.1526 https://doi.org/10.1095/biolreprod62.6.1526

Dunk CE , van Dijk M , Choudhury R , et al. , 2021 . Functional evaluation of STOX1 (STORKHEAD-BOX PROTEIN 1) in placentation, preeclampsia, and preterm birth . Hypertension , 77 ( 2 ): 475 - 490 . https://doi.org/10.1161/HYPERTENSIONAHA.120.15619 https://doi.org/10.1161/HYPERTENSIONAHA.120.15619

Farmer DT , Nathan S , Finley JK , et al. , 2017 . Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland . Development , 144 ( 13 ): 2517 - 2528 . https://doi.org/10.1242/dev.150789 https://doi.org/10.1242/dev.150789

Fearon U , Mullan R , Markham T , et al. , 2006 . Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures . Arthritis Rheum , 54 ( 10 ): 3152 - 3162 . https://doi.org/10.1002/art.22161 https://doi.org/10.1002/art.22161

Fowden AL , Coan PM , Angiolini E , et al. , 2011 . Imprinted genes and the epigenetic regulation of placental phenotype . Prog Biophys Mol Biol , 106 ( 1 ): 281 - 288 . https://doi.org/10.1016/j.pbiomolbio.2010.11.005 https://doi.org/10.1016/j.pbiomolbio.2010.11.005

Garfield AS , Cowley M , Smith FM , et al. , 2011 . Distinct physiological and behavioural functions for parental alleles of imprinted Grb10 . Nature , 469 : 534 - 538 . https://doi.org/10.1038/nature09651 https://doi.org/10.1038/nature09651

Guo J , He H , Liu Q , et al. , 2015 . Identification and epigenetic analysis of a maternally imprinted gene Qpct . Mol Cells , 38 ( 10 ): 859 - 865 . https://doi.org/10.14348/molcells.2015.0098 https://doi.org/10.14348/molcells.2015.0098

Guo L , Li SY , Ji FY , et al. , 2014 . Role of Angptl4 in vascular permeability and inflammation . Inflamm Res , 63 ( 1 ): 13 - 22 . https://doi.org/10.1007/s00011-013-0678-0 https://doi.org/10.1007/s00011-013-0678-0

Haig D , 2014 . Coadaptation and conflict, misconception and muddle, in the evolution of genomic imprinting . Heredity (Edinb) , 113 ( 2 ): 96 - 103 . https://doi.org/10.1038/hdy.2013.97 https://doi.org/10.1038/hdy.2013.97

Halari CD , Nandi P , Jeyarajah MJ , et al. , 2020 . Decorin production by the human decidua: role in decidual cell maturation . Mol Hum Reprod , 26 ( 10 ): 784 - 796 . https://doi.org/10.1093/molehr/gaaa058 https://doi.org/10.1093/molehr/gaaa058

Hemberger M , Hanna CW , Dean W , 2020 . Mechanisms of early placental development in mouse and humans . Nat Rev Genet , 21 : 27 - 43 . https://doi.org/10.1038/s41576-019-0169-4 https://doi.org/10.1038/s41576-019-0169-4

Hiby SE , Lough M , Keverne EB , et al. , 2001 . Paternal monoallelic expression of PEG3 in the human placenta . Hum Mol Genet , 10 ( 10 ): 1093 - 1100 . https://doi.org/10.1093/hmg/10.10.1093 https://doi.org/10.1093/hmg/10.10.1093

Hong J , Qu P , Wuest TR , et al. , 2019 . Neutrophilic granule protein is a novel murine LPS antagonist . Immune Netw , 19 ( 5 ): e34 . https://doi.org/10.4110/in.2019.19.e34 https://doi.org/10.4110/in.2019.19.e34

Hou J , Zhang J , Cui P , et al. , 2021 . TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis . J Clin Invest , 131 ( 4 ): e135197 . https://doi.org/10.1172/JCI135197 https://doi.org/10.1172/JCI135197

Hu W , Chien SY , Ying P , et al. , 2020 . Impact of CCL4 gene polymorphisms upon the progression of lung cancer in a Han Chinese cohort . Medicine (Baltimore) , 99 ( 3 ): e18906 . https://doi.org/10.1097/MD.0000000000018906 https://doi.org/10.1097/MD.0000000000018906

Ikeuchi M , Matsusaka H , Kang D , et al. , 2005 . Overexpression of mitochondrial transcription factor A ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction . Circulation , 112 ( 5 ): 683 - 690 . https://doi.org/10.1161/CIRCULATIONAHA.104.524835 https://doi.org/10.1161/CIRCULATIONAHA.104.524835

Jaipersad AS , Lip GY , Silverman S , et al. , 2014 . The role of monocytes in angiogenesis and atherosclerosis . J Am Coll Cardiol , 63 ( 1 ): 1 - 11 . https://doi.org/10.1016/j.jacc.2013.09.019 https://doi.org/10.1016/j.jacc.2013.09.019

Jaitin DA , Adlung L , Thaiss CA , et al. , 2019 . Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner . Cell , 178 ( 3 ): 686 - 698.e14 . https://doi.org/10.1016/j.cell.2019.05.054 https://doi.org/10.1016/j.cell.2019.05.054

Jakubzick CV , Randolph GJ , Henson PM , 2017 . Monocyte differentiation and antigen-presenting functions . Nat Rev Immunol , 17 ( 6 ): 349 - 362 . https://doi.org/10.1038/nri.2017.28 https://doi.org/10.1038/nri.2017.28

Jiao B , Liu S , Tan X , et al. , 2021 . Class-3 semaphorins: potent multifunctional modulators for angiogenesis-associated diseases . Biomed Pharmacother , 137 : 111329 . https://doi.org/10.1016/j.biopha.2021.111329 https://doi.org/10.1016/j.biopha.2021.111329

Jin S , Guerrero-Juarez CF , Zhang L , et al. , 2021 . Inference and analysis of cell-cell communication using CellChat . Nature Communications , 12 : 1088 . https://doi.org/10.1038/s41467-021-21246-9 https://doi.org/10.1038/s41467-021-21246-9

Korkolopoulou P , Cordell J , Jones M , et al. , 1994 . The expression of the B-cell marker mb-1 (CD79a) in Hodgkin’s disease . Histopathology , 24 ( 6 ): 511 - 515 . https://doi.org/10.1111/j.1365-2559.1994.tb00568.x https://doi.org/10.1111/j.1365-2559.1994.tb00568.x

Kuo CY , Shevchuk M , Opfermann J , et al. , 2019 . Trophoblast-endothelium signaling involves angiogenesis and apoptosis in a dynamic bioprinted placenta model . Biotechnol Bioeng , 116 ( 1 ): 181 - 192 . https://doi.org/10.1002/bit.26850 https://doi.org/10.1002/bit.26850

Larson SR , Atif SM , Gibbings SL , et al. , 2016 . Ly6C + monocyte efferocytosis and cross-presentation of cell-associated antigens . Cell Death Differ , 23 ( 6 ): 997 - 1003 . https://doi.org/10.1038/cdd.2016.24 https://doi.org/10.1038/cdd.2016.24

Li TJ , Jiang YM , Hu YF , et al. , 2017 . Interleukin-17-producing neutrophils link inflammatory stimuli to disease progression by promoting angiogenesis in gastric cancer . Clin Cancer Res , 23 ( 6 ): 1575 - 1585 . https://doi.org/10.1158/1078-0432.CCR-16-0617 https://doi.org/10.1158/1078-0432.CCR-16-0617

Li WV , Li Y , 2021 . ScLink: inferring sparse gene co-expression networks from single-cell expression data . Genomics Proteomics Bioinformatics , 19 ( 3 ): 475 - 492 . https://doi.org/10.1016/j.gpb.2020.11.006 https://doi.org/10.1016/j.gpb.2020.11.006

Liao YY , Tsai HC , Chou PY , et al. , 2016 . CCL3 promotes angiogenesis by dysregulation of miR-374b/VEGF-A axis in human osteosarcoma cells . Oncotarget , 7 ( 4 ): 4310 - 4325 . https://doi.org/10.18632/oncotarget.6708 https://doi.org/10.18632/oncotarget.6708

Liu Y , Fan X , Wang R , et al. , 2018 . Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta . Cell Res , 28 ( 8 ): 819 - 832 . https://doi.org/10.1038/s41422-018-0066-y https://doi.org/10.1038/s41422-018-0066-y

Mann MR , Lee SS , Doherty AS , et al. , 2004 . Selective loss of imprinting in the placenta following preimplantation development in culture . Development , 131 ( 15 ): 3727 - 3735 . https://doi.org/10.1242/dev.01241 https://doi.org/10.1242/dev.01241

Marsh B , Blelloch R , 2020 . Single nuclei RNA-seq of mouse placental labyrinth development . Elife , 9 : e60266 . https://doi.org/10.7554/eLife.60266 https://doi.org/10.7554/eLife.60266

Mayer W , Hemberger M , Frank HG , et al. , 2000 . Expression of the imprinted genes MEST / Mest in human and murine placenta suggests a role in angiogenesis . Dev Dyn , 217 ( 1 ): 1 - 10 . https://doi.‍org/10.‍1002/(SICI)1097-0177(200001)217:1%3C1::AID-DVDY1%3E3.0.CO;2-4 https://doi.‍org/10.‍1002/(SICI)1097-0177(200001)217:1%3C1::AID-DVDY1%3E3.0.CO;2-4

McCoy MG , Nascimento DW , Veleeparambil M , et al. , 2021 . Endothelial TLR2 promotes proangiogenic immune cell recruitment and tumor angiogenesis . Sci Signal , 14 ( 666 ): eabc5371 . https://doi.org/10.1126/scisignal.abc5371 https://doi.org/10.1126/scisignal.abc5371

McDonald LE , Paterson CA , Kay GF , 1998 . Bisulfite genomic sequencing-derived methylation profile of the Xist gene throughout early mouse development . Genomics , 54 ( 3 ): 379 - 386 . https://doi.org/10.1006/geno.1998.5570 https://doi.org/10.1006/geno.1998.5570

Medaglia C , Giladi A , Stoler-Barak L , et al. , 2017 . Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq . Science , 358 ( 6370 ):‍ 1622 - 1626 . https://doi.org/10.1126/science.aao4277 https://doi.org/10.1126/science.aao4277

Menezes S , Melandri D , Anselmi G , et al. , 2016 . The het erogeneity of Ly6C hi monocytes controls their differentiation into iNOS + macrophages or monocyte-derived dendritic cells . Immunity , 45 ( 6 ): 1205 - 1218 . https://doi.org/10.1016/j.immuni.2016.12.001 https://doi.org/10.1016/j.immuni.2016.12.001

Miozzo M , Grati FR , Bulfamante G , et al. , 2001 . Post-zygotic origin of complete maternal chromosome 7 isodisomy and consequent loss of placental PEG1 / MEST expression . Placenta , 22 ( 10 ): 813 - 821 . https://doi.org/10.1053/plac.2001.0728 https://doi.org/10.1053/plac.2001.0728

Moncho-Amor V , Ibanez de Caceres I , Bandres E , et al. , 2011 . DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer . Oncogene , 30 ( 6 ): 668 - 678 . https://doi.org/10.1038/onc.2010.449 https://doi.org/10.1038/onc.2010.449

Moussad EE , Rageh MA , Wilson AK , et al. , 2002 . Temporal and spatial expression of connective tissue growth factor (CCN2; CTGF) and transforming growth factor β type 1 (TGF-β1) at the utero-placental interface during early pre gnancy in the pig. Mol Pathol , 55 ( 3 ): 186 - 192 . https://doi.org/10.1136/mp.55.3.186 https://doi.org/10.1136/mp.55.3.186

Nelson AC , Mould AW , Bikoff EK , et al. , 2016 . Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy . Nat Commun , 7 : 11414 . https://doi.org/10.1038/ncomms11414 https://doi.org/10.1038/ncomms11414

Ngo HB , Kaiser JT , Chan DC , 2011 . The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA . Nat Struct Mol Biol , 18 ( 11 ): 1290 - 1296 . https://doi.org/10.1038/nsmb.2159 https://doi.org/10.1038/nsmb.2159

Okae H , Hiura H , Nishida Y , et al. , 2012 . Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression . Hum Mol Genet , 21 ( 3 ): 548 - 558 . https://doi.org/10.1093/hmg/ddr488 https://doi.org/10.1093/hmg/ddr488

Olsson A , Venkatasubramanian M , Chaudhri VK , et al. , 2016 . Single-cell analysis of mixed-lineage states leading to a binary cell fate choice . Nature , 537 ( 7622 ): 698 - 702 . https://doi.org/10.1038/nature19348 https://doi.org/10.1038/nature19348

Outhwaite JE , McGuire V , Simmons DG , 2015 . Genetic ablation of placental sinusoidal trophoblast giant cells causes fetal growth restriction and embryonic lethality . Placenta , 36 ( 8 ): 951 - 955 . https://doi.org/10.1016/j.placenta.2015.05.013 https://doi.org/10.1016/j.placenta.2015.05.013

Pantouris G , Ho J , Shah D , et al. , 2018 . Nanosecond dynamics regulate the MIF-induced activity of CD74 . Angew Chem Int Ed Engl , 57 ( 24 ): 7116 - 7119 . https://doi.org/10.1002/anie.201803191 https://doi.org/10.1002/anie.201803191

Parkins A , Skeens E , McCallum CM , et al. , 2021 . The N-terminus of MIF regulates the dynamic profile of residues involved in CD74 activation . Biophys J , 120 ( 18 ): 3893 - 3900 . https://doi.org/10.1016/j.bpj.2021.08.025 https://doi.org/10.1016/j.bpj.2021.08.025

Peters J , 2014 . The role of genomic imprinting in biology and disease: an expanding view . Nat Rev Genet , 15 ( 8 ): 517 - 530 . https://doi.org/10.1038/nrg3766 https://doi.org/10.1038/nrg3766

Picton LD , Bertuzzi M , Pallucchi I , et al. , 2021 . A spinal organ of proprioception for integrated motor action feedback . Neuron , 109 ( 7 ): 1188 - 1201.e7 . https://doi.org/10.1016/j.neuron.2021.01.018 https://doi.org/10.1016/j.neuron.2021.01.018

Pique-Regi R , Romero R , Tarca AL , et al. , 2019 . Single cell transcriptional signatures of the human placenta in term and preterm parturition . Elife , 8 : e52004 . https://doi.org/10.7554/eLife.52004 https://doi.org/10.7554/eLife.52004

Plagge A , Gordon E , Dean W , et al. , 2004 . The imprinted signaling protein XLαs is required for postnatal adaptation to feeding . Nat Genet , 36 ( 8 ): 818 - 826 . https://doi.org/10.1038/ng1397 https://doi.org/10.1038/ng1397

Plasschaert RN , Bartolomei MS , 2015 . Tissue-specific regulation and function of Grb10 during growth and neuronal commitment . Proc Natl Acad Sci USA , 112 ( 22 ): 6841 - 6847 . https://doi.org/10.1073/pnas.1411254111 https://doi.org/10.1073/pnas.1411254111

Prissette M , El-Maarri O , Arnaud D , et al. , 2001 . Methylation profiles of DXPas34 during the onset of X-inactivation . Hum Mol Genet , 10 ( 1 ): 31 - 38 . https://doi.org/10.1093/hmg/10.1.31 https://doi.org/10.1093/hmg/10.1.31

Sandovici I , Georgopoulou A , Perez-Garcia V , et al. , 2022 . The imprinted Igf2 - Igf2r axis is critical for matching placental microvasculature expansion to fetal growth . Dev Cell , 57 ( 1 ): 63 - 79.e8 . https://doi.org/10.1016/j.devcel.2021.12.005 https://doi.org/10.1016/j.devcel.2021.12.005

Sasaki H , Kurotaki D , Tamura T , 2016 . Regulation of basophil and mast cell development by transcription factors . Allergol Int , 65 ( 2 ): 127 - 134 . https://doi.org/10.1016/j.alit.2016.01.006 https://doi.org/10.1016/j.alit.2016.01.006

Sferruzzi-Perri AN , Higgins JS , Vaughan OR , et al. , 2019 . Placental mitochondria adapt developmentally and in response to hypoxia to support fetal growth . Proc Natl Acad Sci USA , 116 ( 5 ): 1621 - 1626 . https://doi.org/10.1073/pnas.1816056116 https://doi.org/10.1073/pnas.1816056116

Shiura H , Ono R , Tachibana S , et al. , 2021 . Peg10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta . Development , 148 ( 19 ): dev199564 . https://doi.org/10.1242/dev.199564 https://doi.org/10.1242/dev.199564

Singh H , Endo Y , Nie G , 2011 . Decidual HtrA3 negatively regulates trophoblast invasion during human placentation . Hum Reprod , 26 ( 4 ): 748 - 757 . https://doi.org/10.1093/humrep/der019 https://doi.org/10.1093/humrep/der019

Slyper M , Porter CBM , Ashenberg O , et al. , 2020 . A single-cell and single-nucleus RNA-seq toolbox for fresh and frozen human tumors . Nat Med , 26 ( 5 ): 792 - 802 . https://doi.org/10.1038/s41591-020-0844-1 https://doi.org/10.1038/s41591-020-0844-1

Stoeckius M , Hafemeister C , Stephenson W , et al. , 2017 . Simultaneous epitope and transcriptome measurement in single cells . Nat Methods , 14 ( 9 ): 865 - 868 . https://doi.org/10.1038/nmeth.4380 https://doi.org/10.1038/nmeth.4380

Strickland LA , Jubb AM , Hongo JA , et al. , 2005 . Plasmalemmal vesicle-associated protein (PLVAP) is expressed by tumour endothelium and is upregulated by vascular endothelial growth factor-A (VEGF) . J Pathol , 206 ( 4 ): 466 - 475 . https://doi.org/10.1002/path.1805 https://doi.org/10.1002/path.1805

Sullivan BM , Liang HE , Bando JK , et al. , 2011 . Genetic analysis of basophil function in vivo . Nat Immunol , 12 ( 6 ): 527 - 535 . https://doi.org/10.1038/ni.2036 https://doi.org/10.1038/ni.2036

Sumi Y , Muramatsu H , Takei Y , et al. , 2002 . Midkine, a heparin-binding growth factor, promotes growth and glycosaminoglycan synthesis of endothelial cells through its action on smooth muscle cells in an artificial blood vessel model . J Cell Sci , 115 ( Pt 13 ): 2659 - 2667 . https://doi.org/10.1242/jcs.115.13.2659 https://doi.org/10.1242/jcs.115.13.2659

Suryawanshi H , Morozov P , Straus A , et al. , 2018 . A single-cell survey of the human first-trimester placenta and decidua . Sci Adv , 4 ( 10 ): eaau4788 . https://doi.org/10.1126/sciadv.aau4788 https://doi.org/10.1126/sciadv.aau4788

Thomas JR , Appios A , Zhao X , et al. , 2021 . Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells . J Exp Med , 218 ( 1 ): e20200891 . https://doi.org/10.1084/jem.20200891 https://doi.org/10.1084/jem.20200891

Torres A , Gubbiotti MA , Iozzo RV , 2017 . Decorin-inducible Peg3 evokes Beclin 1-mediated autophagy and Thrombospondin 1-mediated angiostasis . J Biol Chem , 292 ( 12 ): 5055 - 5069 . https://doi.org/10.1074/jbc.M116.753632 https://doi.org/10.1074/jbc.M116.753632

Trzebanski S , Jung S , 2020 . Plasticity of monocyte development and monocyte fates . Immunol Lett , 227 : 66 - 78 . https://doi.org/10.1016/j.imlet.2020.07.007 https://doi.org/10.1016/j.imlet.2020.07.007

Tucci V , Isles AR , Kelsey G , et al. , 2019 . Genomic imprinting and physiological processes in mammals . Cell , 176 ( 5 ): 952 - 965 . https://doi.org/10.1016/j.cell.2019.01.043 https://doi.org/10.1016/j.cell.2019.01.043

Tunster SJ , van de Pette M , John RM , 2011 . Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome . Dis Model Mech , 4 ( 6 ): 814 - 821 . https://doi.org/10.1242/dmm.007328 https://doi.org/10.1242/dmm.007328

Tunster SJ , Creeth HDJ , John RM , 2016 . The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources . Dev Biol , 409 ( 1 ): 251 - 260 . https://doi.org/10.1016/j.ydbio.2015.10.015 https://doi.org/10.1016/j.ydbio.2015.10.015

Uemura A , Fruttiger M , D'Amore PA , et al. , 2021 . VEGFR1 signaling in retinal angiogenesis and microinflammation . Prog Retin Eye Res , 84 : 100954 . https://doi.org/10.1016/j.preteyeres.2021.100954 https://doi.org/10.1016/j.preteyeres.2021.100954

van der Vorst EP , Doring Y , Weber C , 2015 . MIF and CXCL12 in cardiovascular diseases: functional differences and similarities . Front Immunol , 6 : 373 . https://doi.org/10.3389/fimmu.2015.00373 https://doi.org/10.3389/fimmu.2015.00373

Varrault A , Gueydan C , Delalbre A , et al. , 2006 . Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth . Dev Cell , 11 ( 5 ): 711 - 722 . https://doi.org/10.1016/j.devcel.2006.09.003 https://doi.org/10.1016/j.devcel.2006.09.003

Veillat V , Carli C , Metz CN , et al. , 2010 . Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways . J Clin Endocrinol Metab , 95 ( 12 ): E403 - 412 . https://doi.org/10.1210/jc.2010-0417 https://doi.org/10.1210/jc.2010-0417

Vento-Tormo R , Efremova M , Botting RA , et al. , 2018 . Single-cell reconstruction of the early maternal-fetal interface in humans . Nature , 563 : 347 - 353 . https://doi.org/10.1038/s41586-018-0698-6 https://doi.org/10.1038/s41586-018-0698-6

Wang XM , Abraham S , McKenzie JAG , et al. , 2013 . LRG1 promotes angiogenesis by modulating endothelial TGF-‍β signalling . Nature , 499 ( 7458 ): 306 - 311 . https://doi.org/10.1038/nature12345 https://doi.org/10.1038/nature12345

Weckbach LT , Groesser L , Borgolte J , et al. , 2012 . Midkine acts as proangiogenic cytokine in hypoxia-induced angiogenesis . Am J Physiol Heart Circ Physiol , 303 ( 4 ): H429 - 438 . https://doi.org/10.1152/ajpheart.00934.2011 https://doi.org/10.1152/ajpheart.00934.2011

Xu B , Chen X , Ding Y , et al. , 2020 . Abnormal angiogenesis of placenta in progranulindeficient mice . Mol Med Rep , 22 ( 4 ): 3482 - 3492 . https://doi.org/10.3892/mmr.2020.11438 https://doi.org/10.3892/mmr.2020.11438

Xu Y , Luo X , Fang Z , et al. , 2018 . Transcription coactivator cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of bmp signaling . Cell Death Dis , 9 ( 9 ): 924 . https://doi.org/10.1038/s41419-018-0991-1 https://doi.org/10.1038/s41419-018-0991-1

Yan J , Gao Y , Lin S , et al. , 2021 . EGR1-CCL2 feedback loop maintains epithelial-mesenchymal transition of cisplatin-resistant gastric cancer cells and promotes tumor angiogenesis . Dig Dis Sci , 67 : 3702 - 3713 . https://doi.org/10.1007/s10620-021-07250-5 https://doi.org/10.1007/s10620-021-07250-5

Zhang X , Lan Y , Xu J , et al. , 2019 . Cellmarker: a manually curated resource of cell markers in human and mouse . Nucleic Acids Res , 47 ( D1 ): D721 - D728 . https://doi.org/10.1093/nar/gky900 https://doi.org/10.1093/nar/gky900

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Bin YU

Huihui WANG

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Related Institution

Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University

Department of Chinese Integrative Medicine, Women’s Hospital, School of Medicine, Zhejiang University

Department of Radiology, Women’s Hospital, School of Medicine, Zhejiang University

School of Obstetrics and Gynecology, Zhejiang University School of Medicine

Department of Radiology, the Second Hospital of Jilin University

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